Surface-induced platelet activation and subsequent thrombus formation has been a major obstacle to the perfection of blood-contacting artificial organs. The ideal biomaterial would be the one which does not allow platelet adhesion at all. The main goal of this proposal is to test the hypothesis that protein adsorption and platelet adhesion to biomaterials can be prevented by long-range steric repulsion originating from water-soluble polymers grafted to the surface. The specific aims of this study are: (1) to prepare surfaces grafted with various water-soluble polymers (i.e., diffuse surfaces); (2) to analyze protein adsorption and platelet activation on the diffuse surfaces based on the steric repulsion mechanism; (3) to enhance our understanding on the mechanisms of protein adsorption using computer simulations; and (4) to present a unified theory on the prevention of platelet adhesion onto biomaterial surfaces. Highly water-soluble polymers, such as polyethylene oxide (PEO), polyvinylpyrrolidone, dextran, albumin, and gelatin, will be grafted to the model surfaces by radio frequency plasma polymerization and graft coupling methods. The surface coverage by grafted polymers and the thickness of diffuse layers will be varied. Specific emphasis will be given to the grafting of PEO. An efficient means to couple PEO to the surfaces will be developed by synthesizing PEO-containing amphipathic block copolymers with photo-reactive coupling groups. The prepared diffuse surfaces will be characterized by contact angle, ATR-FTIR, ESCA, ellipsometry, and protein adsorption. Platelet behavior on the prepared surfaces will be analyzed by examining morphological changes, cytoskeletal restructuring, and clustering of fibrinogen receptors. The minimum thickness of the diffuse layer necessary for preventing protein adsorption will be examined by calculating the protein-surface interaction energy as a function of distance from the surface. The importance of this research is that it establishes a general theory on the prevention of protein adsorption and platelet adhesion to the biomaterials, and provides guidelines for the preparation of surfaces which are not recognizable by platelets.